Medicine and Health Sciences Commons^™

Editorial: Molecular Mechanisms Of Ion Channel Activation And Modulation, Meng Cui, Miao Zhang

Pharmacy Faculty Articles and Research

"Ion channels are integral membrane proteins that regulate the passage of ions across cell membranes, thereby shaping processes as diverse as neuronal signaling, muscle contraction, and hormone secretion. Channel activation is typically initiated by a stimulus such as voltage, ligand binding, or mechanical stress that induces conformational changes and opens the channel pore. Beyond activation, channels are subject to fine-tuned modulation by a wide range of endogenous and exogenous agents, from lipids and neurotransmitters to pharmacological drugs. Modulators can stabilize the open, closed, or inactivated states, shift ligand affinities, or alter gating kinetics. Dissecting the structural and dynamic basis of …

Grit, A Component Of Resident Well-Being, Nathan W. Olson, Kelly Williamson, Nicholas Hartman, Navneet Cheema, Adriana S. Olson

Journal of Wellness

Introduction: Trainees experiencing burnout, depression, or career dissatisfaction challenge educators and may have patient care consequences. Grit, defined as the “perseverance and passion for long-term goals,” buffers against hopelessness and quantifies an aspect of personality shown to predict fewer career changes. Higher grit has been associated with positive outcomes in physicians, including lower burnout rates. Our objective was to determine the correlation between emergency medicine (EM) resident Short Grit Scale (Grit-S) scores and components of well-being: burnout, a positive depression screen, and career satisfaction.

Methods: This was a prospective, multicenter trial involving ten urban/suburban EM residencies. The subjects …

Chronic Poppers Maculopathy: Case Report And Literature Comparison Of Chronic And Acute Use, Francesco Cappellani, Caterina Gagliano, Jose S. Pulido

Wills Eye Hospital Papers

RATIONALE: Alkyl nitrites ("poppers") are recreational substances known for their vasodilatory and euphoric effects. Increasing evidence links them to a vision-threatening condition termed poppers maculopathy, characterized by foveal yellow spots and outer retinal changes on optical coherence tomography. While most reports describe acute exposure, little is known about long-term consequences. This case describes one of the longest documented durations of chronic poppers use, combined with a literature review to contextualize the clinical spectrum.

PATIENT CONCERNS: A 68-year-old man with human immunodeficiency virus, type 2 diabetes, hypertension, and depression presented with progressive central vision loss in both eyes persisting for at …

Gait Analysis In Rett Syndrome: Integrating Linear And Nonlinear Techniques, Dacia Martinez Diaz, Brock Futrell, Bernhard Suter, Charles S Layne

Faculty, Staff and Students Publications

Rett syndrome is a rare neurodevelopmental disorder that significantly impairs bipedal postural control and walking ability. This study quantifies the gait characteristics of 22 females with Rett syndrome (divided into 3 age groups) and compares them with age-matched neurotypical females. Bilateral sagittal plane joint angles of the hip, knee, and ankle were analyzed. Measures included joint range of motion, stride time, peak angular velocity, angle-angle diagrams, phase portrait areas, and asymmetries. Results revealed reduced joint range of motion and angular velocity in individuals with Rett syndrome, as well as greater asymmetries in gait parameters reflecting disruptions in bilateral coordination. Phase …

Human Cerebral Organoids Model Tumor Initiation And Infiltration In An Autologous Astrocyte-Supported Setting, Esther Schickel, Tamara Bender, Leon Kaysan, Simone Hufgard, Margot Mayer, David R Grosshans, Christiane Thielemann, Insa S Schroeder

Faculty, Staff and Student Publications

Efforts to efficiently target brain tumors are constrained by the dearth of appropriate models to study tumor behavior toward treatment approaches as well as potential side effects to the surrounding normal tissue. We established a reproducible cerebral organoid model of brain tumorigenesis in an autologous setting by overexpressing

Epac1 Deletion Attenuates Müller Glial Pathological Activation And Mitigates Retinal Neurodegeneration In Ischemia-Induced Retinopathy, Shuizhen Shi, Fan Xia, Zhongqiao Lu, Erick Palacios, Fang Mei, Massoud Motamedi, Xiaodong Cheng, Hua Liu, Wenbo Zhang

The Brown Foundation: Institute of Molecular Medicine

Introduction: Ischemia-induced retinopathies, such as retinopathy of prematurity and proliferative diabetic retinopathy, are major causes of vision loss. Both pathological neovascularization and neuronal damage contribute to vision impairment in these conditions, yet current therapies primarily target neovascularization and may further compromise neuronal health.

Objectives: Cyclic AMP (cAMP) is a widely recognized second messenger regulating diverse physiological and pathological processes. Exchange protein directly activated by cAMP (Epac) is a recently identified effector of cAMP signaling. This study aimed to investigate the role of Epac1 in ischemia-induced retinopathy and elucidate its underlying mechanisms using a mouse model of oxygen-induced retinopathy (OIR).

Methods: …

Two Essays On Health And Health Behavior In China, Jiamin Tan

Lingnan Theses (MPhil & PhD)

This thesis consists of two empirical studies on elderly mental health and on health behaviors. The first study investigates the long-term impact of childhood hunger on mental health in later life, using data from two nationally representative surveys in China. The study finds that childhood hunger exposure significantly increases the risks of depression and anxiety in later life. These effects are most pronounced among individuals exposed after age 5, suggesting that autobiographical memory formation plays an important role beyond socioeconomic and health pathways. The findings further indicate these impacts can be mitigated through economic interventions, such as welfare programs, and …

Prenatal Metabolomics Analysis And Fetal Congenital Anomalies And Genetic Conditions: A Review Of Current Literature, Sarah Araji, Onur Turkoglu, Mohamad Ali Maktabi, Tracy Ashby, Ignatia B Van Den Veyver

Library Staff Publications

Fetal congenital anomalies and genetic disorders complicate 3%-5% of pregnancies and can have a significant impact on pregnancy outcomes. Precise and individualized prenatal diagnosis is crucial for effective counseling and management. The identification of new biomarkers holds promise for enhancing prenatal screening, diagnosis, and prognostic counseling in affected pregnancies. Recently, metabolomics has emerged as a potential adjunct in the interpretation of genetic variants identified through genome-wide sequencing for rare genetic conditions. To assess the potential of metabolomic profiling as a functional assay capable of providing deeper insights into the pathological processes and genetic findings associated with prenatal congenital anomalies, we …

Blue-Shifted Ancyromonad Channelrhodopsins For Multiplex Optogenetics, Elena G Govorunova, Oleg A Sineshchekov, Hai Li, Yueyang Gou, Hongmei Chen, Shuyuan Yang, Yumei Wang, Stephen Mitchell, Alyssa Palmateer, Leonid S Brown, François St-Pierre, Mingshan Xue, John L Spudich

Duncan NRI Faculty and Staff Publications

Light-gated ion channels from protists (channelrhodopsins or ChRs) are optogenetic tools widely used for controlling neurons and cardiomyocytes. Multiplex optogenetic applications require spectrally separated molecules, which are difficult to engineer without disrupting channel function. Scanning numerous sequence databases, we identified three naturally blue-shifted ChRs from ancyromonads. They form a separate branch on the phylogenetic tree and contain residue motifs characteristic of anion ChRs (ACRs). However, only two conduct chloride, whereas the closely related Nutomonas longa homolog generates inward cation currents in mammalian cells under physiological conditions, significantly exceeding those by previously known tools with similar spectral maxima (peak absorption at …

Protocol For Non-Invasive Pulsed-Doppler Evaluation Of Blood Flow In The Mouse Ophthalmic Artery, Radwa Awad, Emil Martin, Anilkumar K Reddy, Iraida Sharina

Faculty, Staff and Student Publications

The number of reliable and non-invasive techniques to characterize ocular blood flow is limited. Here, we present a protocol for identifying a soft tissue window in the orbital aperture using pulsed-Doppler ultrasonography to offer real-time, non-invasive blood flow velocity monitoring in the mouse ophthalmic artery. We describe steps for preparing a mouse, positioning the ultrasound probe, and acquiring and recording signals. We then detail procedures for analyzing results using a workstation equipped with Doppler flow velocity software. For complete details on the use and execution of this protocol, please refer to Sharina et al.

Metabolic Shifts In Murine Inner Ears Mimicking Erythrocytes And Plasma Reveal Diagnostics And Early Predictors For Age-Related Hearing Loss, Qi Guo, Zhenjiang Li, Cheng Luo, Changhan Chen, Xi Long, Yidan Wang, Qingfen Qiang, Fang Yu, Wuping Liu, Yujin Zhang, Rodney E Kellems, Yang Xia

Faculty, Staff and Student Publications

Age-related hearing loss (ARHL) is a major public health concern, driven by the interplay of multiple factors. Here, we reveal spatiotemporal metabolic shifts in murine inner ears mirroring erythrocytes and plasma. Isotope-labeled glucose tracing demonstrates a metabolic rerouting favoring glycolysis over the pentose phosphate pathway, alongside downregulation of the tricarboxylic acid cycle, indicating impaired energy production and redox homeostasis. Accumulation of medium- and long-chain acylcarnitines further exacerbates lipotoxicity. Notably, age-dependent depletion of arginine, lysine, proline, and glycine disrupts the arginine-polyamine-urea cycle. Translationally, UK Biobank plasma metabolomics links omega-6 fatty acids, linoleic acid, glycine, and albumin to ARHL resilience, while branched-chain …

Trends And Disparities In Acute Coronary Syndrome-Related Mortality In The United States: Implications For Healthcare, Muhammad Khuzzaim Khan, Ibrahim Ahmed Khan, Abdul Moiz Javed, Arslan Wazir, Hira Saleem, Muhammad Zohaib, Faisal Rasheed, Priyanka Mohan Lal, Syeda Laiba Sherazi, Amiaz Karim, Nikhil Duseja, Hussam Al Hennawi

Abington Jefferson Health Papers

Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the United States (US). However, the trends and disparities in ACS mortality are not well understood. This study aimed to analyze the ACS mortality in the US from 1999 to 2020 using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database. The age-adjusted mortality rates (AAMR) due to ACS were calculated for each year from 1999 to 2020, stratified by sex, race, urbanization, and state. The trends and disparities in AAMR were examined using descriptive statistics and graphical methods. The AAMR due …

Can Predictive And Functional Methods Locate The Dysplastic Hip Joint Center?, Michael Harris, Emma C. Behrman, Keith R. Lohse, Molly C. Shepherd, Bruce A. Macwilliams, Erin M. Mannen

2020-Current year OA Pubs

BACKGROUND: Properly characterizing biomechanics in populations with known hip deformities, such as developmental dysplasia of the hip (DDH), requires accurately identifying the hip joint center (HJC). Many studies have assessed the accuracy or repeatability of predictive and functional methods to locate the HJC in normally shaped hips, but not for hips with DDH.

RESEARCH QUESTION: For patients with DDH, which of three common functional and four common predictive HJC methods is most accurate compared to a magnetic-resonance-imaging-based anatomic method?

METHODS: HJC method accuracy was calculated as the resultant vector distance from the anatomic HJCs. Bias was calculated as distance errors …

Human Single-Neuron Activity Is Modulated By Intracranial Theta Burst Stimulation Of The Basolateral Amygdala, Justin M Campbell, Shuo Wang, Lawrence N Eisenman, James Swift, Tao Xie, Peter Brunner, Jon Timothy Willie, Et Al.

2020-Current year OA Pubs

Direct electrical stimulation of the human brain has been used for numerous clinical and scientific applications. At present, however, little is known about how intracranial stimulation affects activity at the microscale. In this study, we recorded intracranial EEG data from a cohort of patients with medically refractory epilepsy as they completed a visual recognition memory task. During the memory task, brief trains of intracranial theta burst stimulation (TBS) were delivered to the basolateral amygdala (BLA). Using simultaneous microelectrode recordings, we isolated neurons in the hippocampus, amygdala, orbitofrontal cortex, and anterior cingulate cortex and tested whether stimulation enhanced or suppressed firing …

1,2,4-Triazole-Based First-In-Class Non-Nucleoside Inhibitors Of The Bacterial Enzyme Mray, Tomayo Berida, Tzu-Yu Huang, Stefanie C Weck, Marcel Lutz, Samuel R Mckee, Nathalie Kagerah, Destinee L Manning, Mohamed E Jahan, Sushil Mishra, Jennifer Herrmann, Rolf Müller, Robert J Doerksen, Christina L Stallings, Christian Ducho, Sudeshna Roy

2020-Current year OA Pubs

MraY is an essential bacterial enzyme for peptidoglycan synthesis in cell walls and serves as a promising but unrealized target for developing effective antibacterial drugs. Nature has provided a remarkable array of nucleoside inhibitors of MraY, and researchers have skillfully refined these structures to develop inhibitors that effectively mimic natural products. Yet, both natural products and their synthetic variants often face challenges regarding inadequate

Retinopathy Of Prematurity: History, Diagnosis, And Treatment, Henry Nguyen, Bs, Ayra Khan, Bs, Flavius Beca, Md, Yoshihiro Yonekawa, Md

inSIGHT

Abstract
Retinopathy of prematurity (ROP) is a vasoproliferative disorder that remains a leading cause of preventable childhood blindness worldwide. This review examines the current understanding of ROP's pathophysiology, prevention, diagnosis, and treatment. ROP develops in two distinct phases: an initial hyperoxic phase, denoted by decreased levels of vascular endothelial growth factor (VEGF), followed by a hypoxic phase, where increasing levels of VEGF trigger pathological neovascularization. Currently, the most effective therapeutics for management are laser photocoagulation and anti-VEGF therapies. The current paradigm in ROP management is shifting toward earlier identification, better risk stratification, and integration of digital screening technologies and standardizing …

Genetic Counseling In Ophthalmology: An Interview, Emmanuel Worede-Kal, Bs

inSIGHT

Ms. Procopio has been practicing as a genetic counselor for seven years, and in the Department of Ocular Genetics at Wills Eye Hospital for the past four years. She provides patients with information necessary to understand the role of genetic testing and the impact of results on their care as well as potential implications for family members. Given the rapidly changing field of ophthalmic genetics, Ms. Procopio is an important member of the multidisciplinary care team of patients with rare genetic conditions.

Comparing Approaches To Refractive Laser Eye Surgery, Tejal Patel, Ba

inSIGHT

Laser eye surgery is one of the most common outpatient ophthalmic procedures performed in the United States. Most patients choose laser eye surgery because they want to decrease the need for daily glasses or contact lens wear. In the past 10 years, over 700,00 eyes have been treated with some type of laser surgery (1).¹ While colloquially known as “LASIK,” there are three major types of laser eye surgeries: Photorefractive Keratectomy (PRK), Laser in Situ Keratomileusis (LASIK), and Small Incision Lenticule Extraction (SMILE). These surgeries all fundamentally rely on the same concept of using a laser to reshape the …

A Day In The Life Of An Orbital And Oculoplastic Surgeon, Alexis Duffy, Ba

inSIGHT

Have you ever heard of an oculoplastic surgeon before? And if so, ever wonder what they do or how they differ from plastic surgeons? Treating the periocular region requires an in-depth understanding not only of the eye, but also its complex interplay with adjacent orbital, sinus, and craniofacial anatomy; there is much more than meets the eye! The most common pathway to become an oculoplastic surgeon includes completion of a four-year ophthalmology residency, followed by one to two years of subspecialized oculoplastic fellowship. Oculoplastic fellowships provide surgical and medical experience managing pathology of the eyelid and orbit, and different programs …

Idiopathic Intracranial Hypertension: A Comprehensive Review Of Diagnosis And Management, Sriya Sadhu, Bs

inSIGHT

Idiopathic intracranial hypertension (IIH) is a critical vision-threatening disease that has been on the rise over the past 10 years.¹ IIH is a condition involving an increase in intracranial pressure due to an unknown (idiopathic), nonspecific cause. The previous alternative name of IIH, "pseudotumor cerebri" (false brain tumor), was given because IIH can present with symptoms similar to those that are seen in several brain tumors - severe headaches, seizures, nausea, and vision deterioration. IIH has a primarily female predominance and a strong association with obesity. As the rates of obesity increase, the prevalence of IIH is similarly expected …

Recent Trends In The Ophthalmology Match, Michael Pratt, Ma

inSIGHT

Ophthalmology remains a competitive field to match for residency, with applications far outnumbering available positions. The criteria for a successful match are unclear owing to differences in data reporting from the SF Match system as compared to the National Residency Match Program, a relatively low volume of scholarly research about the ophthalmology match, and the transition of the USMLE Step 1 exam to pass/fail grading in 2022. This narrative review, while not intended as a guide to become a competitive applicant for residency, will summarize the 2024 ophthalmology match cycle results, report the specific match rate for Sidney Kimmel Medical …

Vascular, Immunological, And Mechanical Factors In Normal Tension Glaucoma: A Multidimensional Approach To Pathogenesis, Rachel E. Cain

inSIGHT

Glaucoma is characterized by progressive degeneration of retinal ganglion cells leading to optic neuropathy and visual field loss.

The major risk factor for glaucoma is elevated intra-ocular pressure (IOP) (Fig. 1). However, 30-40% of patients with glaucoma have normal IOP, leading to the classification of normal-tension glaucoma (NTG) (Fig. 1 C, E).^1,2 The prevalence of NTG varies between populations, with Asians having the highest prevalence (77- 92%), followed by Africans (57%), and Caucasians (30-39%).³ In a landmark study, the collaborative normal tension glaucoma study group (CNTGS) showed that a 30% reduction in IOP in NTG patients slowed the …

Giving More Than Vision: The Evolution And Impact Of Give Kids Sight Day, Leah Prischak, Bs

inSIGHT

Current literature strongly suggests that quality of life is diminished in children with visual impairments.¹ In many situations, visual impairment (VI) can be a serious barrier in obtaining the typical experiences and accomplishments of childhood. Evidence suggests an association between visual acuity, refractive error, and child academic performance.² VI is also associated with the prevalence of more intangible, psychological obstacles in areas such as independence and autonomy, concerns about the future, social relationships, participation, and acceptance.³

Retina In 10 Years—Exciting Developments, Amer Ahmed

inSIGHT

Significant advancements in the field of retina are expected over the next decade.

Wet AMD: Emerging Therapies
Wet age-related macular degeneration (AMD) is a chronic eye condition and a leading cause of vision loss in older adults. It occurs when abnormal blood vessels grow beneath the macula. These vessels are fragile and prone to leaking blood or fluid, which damages the retina and leads to rapid central vision loss.¹

Insight, Volume 5, Issue 1, 2025

inSIGHT

Contents

8 - Retina in 10 Years—Exciting Developments
By Amer Ahmed

12 - Giving More than Vision: The Evolution and Impact of Give Kids Sight Day
By Leah Prischak

15 - Vascular, Immunological, and Mechanical Factors in Normal Tension Glaucoma: A Multidimensional Approach to Pathogenesis
By Rachel Cain

22 - Recent Trends in the Ophthalmology Match
By Michael Pratt

25 - Idiopathic Intracranial Hypertension: A Comprehensive Review of Diagnosis and Management
By Sriya Sadhu

31 - Day in the Life of an Orbital and Oculoplastic Surgeon
By Alexis Duffy

35 - Idiopathic Intracranial Hypertension
By Tejal Patel

42 - Genetic …

Treatment Of Tics In Pediatric Patients With Neurodevelopmental Disorders, Faiza Ahmad

Research Colloquium

Background: The prevalence of chronic and transient tic disorders in children with neurodevelopmental delays is substantially higher than in the general pediatric population. Disorders including Tourette’s Syndrome, Chronic Persistent Motor Tic Disorder or Provisional Tic Disorder, can present challenges in treatment when comorbid neurodevelopmental disorders. Children with Autism Spectrum Disorder (ASD), Down’s Syndrome or other developmental delays may not be able to participate in first-line behavioral interventions like CBIT (Comprehensive Behavioral Intervention for Tics) therapy. Therefore, optimization of pharmacologic treatment is often necessary in this population, especially in the case of severe, refractory tics. Additionally, pharmacologic treatment can be …

Miconazole Induces Cell Cycle Arrest And Apoptosis In Prostate Cancer Cells Via A P53-Mediated Pathway: A Drug Repurposing Strategy, Eswara Naga Hanuma Kumar Ghali, Lindsey Shim, Rahul Tiwari, Rajasekhar Baru, Anupam Dhasmana, Ryan Chang, Sung Yun Jung, Vivek K. Kashyap, Neeraj Chauhan, Subhash Chauhan, Murali Yallapu

Research Colloquium

Aim: Repurposing of FDA-approved antifungal drugs to combat prostate cancer.

Background: Prostate cancer is one of the leading causes of cancer death among men in the United States, second only to non-melanoma skin cancer. The American Cancer Society estimates about 313,780 new cases and 35,770 deaths from prostate cancer in 2025. Despite various treatments such as radiation therapy (both external beam and internal), chemotherapy, hormone therapy, cryotherapy, biological therapy, and high-intensity focused ultrasound, men are monitored for side effects over many years. Therefore, new drugs and treatment strategies are urgently needed to address this challenge.

Methods: In this study, we …

Bridging Genetics And Pharmacology: Diazoxide Choline Xr (Vykat) In The Treatment Of Hyperphagia In Prader–Willi Syndrome, Elena Dike, Nazia Siddiqui, Astrid-Ines Foamkom, Bharathi Gadad

Research Colloquium

Prader–Willi Syndrome (PWS) is a rare genetic disorder caused by loss of paternal expression in the 15q11–q13 region, with the SNORD116/SNHG14 cluster most strongly linked to hyperphagia. This hyperphagia is a major cause of morbidity in PWS. Vykat, a recently approved FDA drug to treat hyperphagia in PWS acts by opening KATP channels in pancreatic β-cells, thereby reducing insulin secretion and indirectly improving satiety. This presentation aims to highlight the central hypothalamic dysfunction from genetic imprinting defects and the peripheral action of Vykat. While Vykat represents a significant advance, especially for individuals with severe hyperphagia, it does not address the …

Chromoblastomycosis Of The Diabetic Foot: A Diagnostic Challenge, Edwardo Abrego Ii, Laura Ackerman, Mario Trujillo-Acosta

Research Colloquium

Background: Chromoblastomycosis (CBM) is a rare transcutaneous fungal infection, estimated to affect roughly 1 in 8 million Americans annually. CBM is considered an occupational disease in tropical climates for farm workers exposed to contaminated soil/plants. This infection has an insidious onset and can be recurrent, yielding verrucous/nodular lesions that can be mistaken with polymicrobial bacterial infections in diabetic patients. If not promptly diagnosed and treated, CBM can lead to malignant transformation, which places an emphasis on a thorough history as this can influence proper workup.

Case Presentation: A 66-year-old Hispanic insulin-dependent type II diabetic male presented to the …

Hfd Feeding For Seven Months Abolishes Sting Disruption-Driven But Not Female Sex-Based Protection Against Hepatic Steatosis And Inflammation In Mice, Xinlei Guo, Honggui Li, Bilian Zhu, Xiaoxiao Wang, Qian Xu, Eduardo A. Aquino, Minji Koo, Qingsheng Li, James Cai, Shannon Glaser, Chaodong Wu

Research Colloquium

Stimulator of interferon genes (STING) is positively correlated with the degrees of liver inflammation in human metabolic dysfunction-associated steatotic liver disease (MASLD). In addition, STING disruption alleviates MASLD in mice fed a high-fat diet (HFD) for 3 months (3- m-HFD). Here we investigated the role of the duration of dietary feeding in regulating MASLD in mice and explored the involvement of STING in sex differences in MASLD. Both male and female STING-disrupted (STINGgt) and wild-type C57BL/6J mice were fed an HFD for 3 or 7 months (7-m-HFD). Additionally, female STINGgt mice upon ovariectomy (OVX) and 3-m-HFD were analyzed for MASLD. …